Comparison of ICG Microangiography and Conventional Angiography in Severe Frostbite

Frostbite Clinical Trial

Official title:

Prospective Comparison of ICG Microangiography and Conventional Angiography in Severe Frostbite

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05777590
• Other study ID #: A22-321
• Status: Recruiting
• Start date: February 3, 2023
• Est. completion date: March 31, 2025

Study information

• Verified date: February 2024
• Source: HealthPartners Institute
• Contact: Kirsten Dalrymple, PhD
• Phone: 651-254-5316
• Email: kirsten.a.dalrymple[@]healthpartners.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Severe frostbite injury is a significant cause of morbidity in northern climates. Minnesota has some of the highest numbers of severe frostbite injuries in North America. As a result, Regions Hospital has the best opportunity to study this disease process and improve outcomes for frostbite patients. The diagnostic methods for severe frostbite injury vary from institution to institution and there is no standard practice. Commonly utilized methods include conventional angiography, Technetium 99 triple phase bone scans, SPECT studies, Indocyanine Green microangiography, and doppler studies. The proposed pilot study aims to directly compare conventional angiography imaging to ICG microangiography in adult patients with severe frostbite. Severe frostbite is defined as 4th degree: frostbite resulting in vascular occlusion and tissue ischemia. Both imaging modalities have been used for the diagnosis and monitoring of severe frostbite injury but there has never been a study directly comparing these two imaging modalities.

Description:

Frostbite injury has been a significant cause of morbidity and mortality for as long as humans have experienced cold winters. When frostbite occurs, there are two primary mechanisms through which tissue damage occurs, though the main mechanism focused on here is systemic cooling. Frostbite is a multiphase process that starts with systemic cooling. As the body cools, blood is shunted from the extremities to the core to maintain heat in the vital organs. During this shunting, there is extensive vasospasm in the extremities and the tissue becomes ischemic. Upon further cooling, tissue ice crystals form within the cells and interstitial spaces causing desiccation and cell destruction. This occurs in the soft tissues and also affects the endothelium of the micro- and macro-vasculature. Clots form in the microvasculature, worsening the ischemia. All ischemic tissues release pro-inflammatory factors, which increase inflammation and worsen clotting.

Upon rewarming of the frozen tissues, the reperfusion can worsen the inflammatory state as these factors released by the ischemic tissue are now able to circulate. Rapid rewarming is used as a tool to mitigate this reperfusion injury, but it does not eliminate the damage. After rapid rewarming, the tissue is assessed for the extent of damage to determine next treatment steps. Diagnosis varies by institution, but the main goal of all diagnostic modalities is to determine if there is a vascular cutoff causing tissue ischemia.

At Regions Hospital, the main diagnostic method that has been used for over 20 years is conventional angiography. This clearly demonstrates the microvasculature of the tissues and allows the intra-arterial catheter directed sheaths to be placed to start thrombolytics, heparin, and vasodilators to treat the tissue ischemia. Other diagnostic modalities used elsewhere include Technetium 99 triple phase bone scans, SPECT imaging, and indocyanine green (ICG) microangiography. All of these imaging modalities demonstrate the perfusion of the affected tissue but do not allow for directed delivery of thrombolytics. In institutions that use these imaging techniques, thrombolytics are typically delivered in an intravenous fashion rather than intra-arterial.

ICG microangiography is a technology that has had rapidly expanding applications in recent decades. These have included retinal imaging, determining perfusion of colorectal anastomoses, biliary imaging, and assessing the blood supply of tissue flaps. It has recently been used in diagnosis of frostbite with good correlation with severe final amputation levels. It is easy to use, non-radiating, can be performed at the bedside, and cheaper than other imaging modalities.

Given that every hospital has different diagnostic and treatment algorithms, these different imaging modalities have rarely been compared in the same patient. The current best metric is comparing the imaging modality with the amount of tissue that is amputated as demonstrated in prior studies cited here. This research application provides a unique opportunity to compare two imaging modalities head-to-head in the same patient and determine their concordance or discordance.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult (>18 years old) patients

2. Diagnosed with severe frostbite by conventional angiography

3. Undergoing thrombolysis with catheter directed lytics

4. Clinically sober at the time of consent

5. Cognitively able to provide consent as determined by clinician's best judgement

6. Normal kidney function (GFR >60)

Exclusion Criteria:

1. Pregnant. Pregnancy will be determined by standard of care pregnancy test performed on all female frostbite patients who are receiving lytics.

2. Iodine allergy.

Related Conditions & MeSH terms

• Frostbite

Intervention

Drug:
• Indocyanine Green Angiogram
Angiogram using ICG dye the occurs directly after conventional angiogram in assessment of frostbite patients undergoing thrombolysis

Locations

Country	Name	City	State
United States	Regions Hospital	Saint Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
HealthPartners Institute

Country where clinical trial is conducted

United States, 

References & Publications (19)

Bourne MH, Piepkorn MW, Clayton F, Leonard LG. Analysis of microvascular changes in frostbite injury. J Surg Res. 1986 Jan;40(1):26-35. doi: 10.1016/0022-4804(86)90141-1. — View Citation

Braun JD, Trinidad-Hernandez M, Perry D, Armstrong DG, Mills JL Sr. Early quantitative evaluation of indocyanine green angiography in patients with critical limb ischemia. J Vasc Surg. 2013 May;57(5):1213-8. doi: 10.1016/j.jvs.2012.10.113. Epub 2013 Jan 24. — View Citation

Gao Y, Wang F, Zhou W, Pan S. Research progress in the pathogenic mechanisms and imaging of severe frostbite. Eur J Radiol. 2021 Apr;137:109605. doi: 10.1016/j.ejrad.2021.109605. Epub 2021 Feb 17. — View Citation

Gonzaga T, Jenabzadeh K, Anderson CP, Mohr WJ, Endorf FW, Ahrenholz DH. Use of Intra-arterial Thrombolytic Therapy for Acute Treatment of Frostbite in 62 Patients with Review of Thrombolytic Therapy in Frostbite. J Burn Care Res. 2016 Jul-Aug;37(4):e323-34. doi: 10.1097/BCR.0000000000000245. — View Citation

Heard J, Shamrock A, Galet C, Pape KO, Laroia S, Wibbenmeyer L. Thrombolytic Use in Management of Frostbite Injuries: Eight Year Retrospective Review at a Single Institution. J Burn Care Res. 2020 May 2;41(3):722-726. doi: 10.1093/jbcr/iraa028. — View Citation

Jafari MD, Lee KH, Halabi WJ, Mills SD, Carmichael JC, Stamos MJ, Pigazzi A. The use of indocyanine green fluorescence to assess anastomotic perfusion during robotic assisted laparoscopic rectal surgery. Surg Endosc. 2013 Aug;27(8):3003-8. doi: 10.1007/s00464-013-2832-8. Epub 2013 Feb 13. — View Citation

Lacey AM, Fey RM, Gayken JR, Endorf FW, Schmitz KR, Punjabi GV, Masters TC, Nygaard RM. Microangiography: An Alternative Tool for Assessing Severe Frostbite Injury. J Burn Care Res. 2019 Aug 14;40(5):566-569. doi: 10.1093/jbcr/irz112. — View Citation

Lacey AM, Rogers C, Endorf FW, Fey RM, Gayken JR, Schmitz KR, Punjabi GV, Whitley AB, Masters TC, Moore JC, Nygaard RM. An Institutional Protocol for the Treatment of Severe Frostbite Injury-A 6-Year Retrospective Analysis. J Burn Care Res. 2021 Aug 4;42(4):817-820. doi: 10.1093/jbcr/irab008. — View Citation

Masters T, Omodt S, Gayken J, Logue C, Westgard B, Hendriksen S, Walter J, Nygaard R. Microangiography to Monitor Treatment Outcomes Following Severe Frostbite Injury to the Hands. J Burn Care Res. 2018 Jan 1;39(1):162-167. doi: 10.1097/BCR.0000000000000526. — View Citation

McCauley RL, Hing DN, Robson MC, Heggers JP. Frostbite injuries: a rational approach based on the pathophysiology. J Trauma. 1983 Feb;23(2):143-7. — View Citation

Millet JD, Brown RK, Levi B, Kraft CT, Jacobson JA, Gross MD, Wong KK. Frostbite: Spectrum of Imaging Findings and Guidelines for Management. Radiographics. 2016 Nov-Dec;36(7):2154-2169. doi: 10.1148/rg.2016160045. Epub 2016 Aug 5. — View Citation

Nygaard RM, Whitley AB, Fey RM, Wagner AL. The Hennepin Score: Quantification of Frostbite Management Efficacy. J Burn Care Res. 2016 Jul-Aug;37(4):e317-22. doi: 10.1097/BCR.0000000000000277. — View Citation

Robson MC, Heggers JP. Evaluation of hand frostbite blister fluid as a clue to pathogenesis. J Hand Surg Am. 1981 Jan;6(1):43-7. doi: 10.1016/s0363-5023(81)80010-x. — View Citation

Rogers C, Lacey AM, Endorf FW, Punjabi G, Whitley A, Gayken J, Fey R, Schmitz K, Nygaard RM. The Effects of Rapid Rewarming on Tissue Salvage in Severe Frostbite Injury. J Burn Care Res. 2022 Jul 1;43(4):906-911. doi: 10.1093/jbcr/irab218. — View Citation

Rohrer MJ, Natale AM. Effect of hypothermia on the coagulation cascade. Crit Care Med. 1992 Oct;20(10):1402-5. doi: 10.1097/00003246-199210000-00007. — View Citation

Twomey JA, Peltier GL, Zera RT. An open-label study to evaluate the safety and efficacy of tissue plasminogen activator in treatment of severe frostbite. J Trauma. 2005 Dec;59(6):1350-4; discussion 1354-5. doi: 10.1097/01.ta.0000195517.50778.2e. — View Citation

WEATHERLEY-WHITE RC, SJOSTROM B, PATON BC. EXPERIMENTAL STUDIES IN COLD INJURY. II. THE PATHOGENESIS OF FROSTBITE. J Surg Res. 1964 Jan;4:17-22. doi: 10.1016/s0022-4804(64)80004-4. No abstract available. — View Citation

Zhi Z, Yin X, Dziennis S, Wietecha T, Hudkins KL, Alpers CE, Wang RK. Optical microangiography of retina and choroid and measurement of total retinal blood flow in mice. Biomed Opt Express. 2012 Nov 1;3(11):2976-86. doi: 10.1364/BOE.3.002976. Epub 2012 Oct 24. — View Citation

Zook N, Hussmann J, Brown R, Russell R, Kucan J, Roth A, Suchy H. Microcirculatory studies of frostbite injury. Ann Plast Surg. 1998 Mar;40(3):246-53; discussion 254-5. doi: 10.1097/00000637-199803000-00009. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of Angiography and ICG microangiography imaging demonstrating ischemic tissue present in severe frostbite scored by Hennepin Frostbite Score.	Hypothesize that these two imaging modalities (ICG (indocyanine green) and conventional angiography) will be concordant at demonstrating the ischemic tissue present in severe frostbite.	Through study completion, an average of 2 years
Secondary	Safety of indocyanine green when delivered in close association with contrast dye (used in conventional angiography) measured by number of adverse events	Contrast dye used in conventional angiography is associated with nephrotoxicity and other risks. Indocyanine green dye is generally considered to be a highly safe product with minimal risks associated with administration. It has been used for decades with minimal side effects. It is hypothesized that ICG dye will not result in any increase in risk to the patient when delivered in temporal proximity to conventional dye.	Through study completion, an average of 2 years